Median CRP Research Articles

SARS-CoV-2 Infection in Filipino Children: An Interim Report from the SALVACION Registry

Background: The COVID-19 pandemic continues to afflict nations worldwide. The Philippines is no exception which has recorded more than 3 million cases as of December 2021 with children comprising 12% of total cases. Since the start of the pandemic, the Pediatric Infectious Disease Society of the Philippines (PIDSP) has been collecting data nationwide, through an online pediatric COVID-19 registry (SALVACION registry), to provide a better understanding of COVID-19 in children in the local setting. Methods: This was an ambispective cohort study of pediatric COVID-19 cases in the Philippines reported from March 2020 to December 2021. Data on clinical features, laboratory findings, disease severity, and treatment outcomes were voluntarily reported by physicians across the country. This study was approved by the Department of Health Single Joint Research Ethics Board. Results: As of December 30, 2021, there were 2,127 cases reported in the registry, with a median age of 5 years (interquartile range: 1-13 years) and mostly mild (41.9%) or moderate (24.5%) in severity. The top symptoms reported were fever (57.9%), cough (42.7%), coryza/colds (29.4%), anorexia (25.2%), and difficulty of breathing (23.1%). The most common comorbidities were hematologic-oncologic diseases (7.4%), neurologic diseases (7.0%) and surgical conditions (4.4%), while the most common coinfections were sepsis (6.3%), dengue fever (4.8%) and healthcare-associated pneumonia (2.1%). Significantly higher median CRP, procalcitonin, D-dimer, ferritin, transaminases and lactate dehydrogenase were seen among severe/critical cases compared to non-severe cases. There was a high frequency of antibiotic use (58%). Most cases recovered, although 172 deaths were reported with an 8.6% case fatality rate. The most common comorbidities in those who died were neurologic (15.7%), cardiac (12.8%) and hematologic (11.6%) diseases. Conclusion: Children across all age groups are susceptible to COVID-19 and most cases are mild or moderate in severity. Among severe and critical cases, the most common comorbidities were neurologic, hematologic-oncologic and cardiac diseases. Most patients recovered with supportive management.

07 Predictor factors of hip involvement in juvenile idiopathic arthritis

BackgroundJuvenile idiopathic arthritis (JIA) is one of the commonest rheumatic diseases in children. Hip involvement is a common problem in JIA patients and is associated with functional disability and poor outcomes. Intensive therapy is required to avoid joint replacement surgery. Little studied in the literature, the predictors of hip involvement are still unknown.ObjectivesOur study aims to identify the clinical, biological characteristic of patients with hip involvement and determine the associated risk factors.MethodsA cross-sectional study including children with JIA according to the International League of Associations for Rheumatology (ILAR). The recorded data included sociodemographic features, disease characteristics (subtype disease, duration, and juvenile arthritis disease activity score (JADAS)) as well as treatment modalities. Regarding coxitis, we collected radiographs, ultrasound (US), and magnetic resonance imaging (MRI) of the hip when performed. Coxitis was defined by clinical (limited range of motion) and/or radiographic findings (destruction, synovitis, bone marrow oedema).ResultsThirty-five patients (20 females) with a median age of 12 years (5–18) and disease duration of 3 years (0.25–15) were recruited. The patient's distribution of JIA subtypes were oligoarticular (n = 13), enthesitis-related arthritis (n = 9), polyarticular (n = 4) (negative rheumatoid factor in 3 patients), undifferentiated (n = 4), psoriatic-arthritis (n = 4) and systemic-onset (n = 1). ESR and CRP median values were 15 mm/h (0–63) and 2 mg/l(0–47) respectively. Sixteen patients were under DMARDs (Methotrexate (n = 10), biological agent (n = 3), biological agent and methotrexate (n = 2), salazopyrine (n = 1)).Sixteen patients (45.71%) developed coxitis (radiographic (n = 8), MRI (n = 5) and US findings (n = 3)) with eight (50%) presenting limited range of motion and 10 (62.5%) developing radiological evidence of hip damage. Hip involvement was associated with a longer disease duration (p = 0.051). JADAS score value of patients with coxitis was higher (Mean 8.35 vs 7.05) but not significantly (p = 0.565). Higher CRP and ESR values were found in patients with coxitis (mean 8.39 mg/l vs 6.83 mg/l, 22.29 mm/h vs 16.37 mm/h respectively) but not significantly (p = 0.718, p = 0.287 respectively). No associations were found between hip involvement and BMI (p = 0.233), age-onset (p = 0.496), JIA subtype (p = 0.509), nor sex (p = 0.767).ConclusionOur study shows that long disease duration exposes to a higher risk of hip involvement in children with JIA. Active disease and biological inflammatory syndrome could be associated risk factors. Studies with larger sample sizes are needed to draw definite causal associations.

Cutibacterium acnes endocarditis: a multicenter case series

Abstract Background Infective endocarditis (IE) due to Cutibacterium acnes (C. acnes) (formerly known as Propionibacterium acnes) is challenging to diagnose. It is suggested that patients often present without fever nor inflammatory parameters. Meanwhile, cardiac abscesses and valve dysfunction are often reported, with a high percentage of patients requiring cardiac surgery [1–7]. No study has yet confirmed the atypical presentation of IE caused by C. acnes. Purpose To study clinical characteristics and outcomes of patients with C. acnes IE. Methods A multinational retrospective case series was conducted. Patients who were diagnosed with definite IE according to the modified Duke criteria between 2010 and 2020 were included. There were six participating hospitals. Cases were identified by positive blood cultures or positive valve/prosthesis cultures. Clinical data was retrieved from medical records. Results We identified 61 cases of C. acnes IE. Patients were predominantly male (n=58, 95%) and had previous cardiac surgery (n=56, 91.8%), which in most cases consisted of aortic valve replacement or Bentall procedures (n=34, 60.7% and n=13, 23.2% respectively). The median time between index surgery and presentation was 31 months (IQR 15.9–69.3). At presentation, fever was absent in 59% of patients (n=36). Most patients experienced symptoms for one to two weeks prior to hospital presentation (41%). At presentation, the median CRP level was 35.5 mg/L (IQR 10.0–70.8). Moreover, in 23% of patients (n=14), the median CRP level was not elevated (<10.0 mg/L). The median leucocyte count at presentation was 9.8x109/L (IQR 8.0–12.3), and thus not exceeding the upper limit of the normal range (10.0x109/L). Approximately half of the blood cultures became positive. In addition, the median time to positivity of blood cultures was seven days (IQR 6–9) and 82.4% of patients had a time to positivity of more than five days. (Redo) surgery was performed in 40 patients (65.5%). Peroperatively, valve dehiscence was observed in 19 patients (47.5%) and vegetations and abscesses were present in 16 patients (40%). The 30-day and one-year mortality rates were 4.9% and 11.5% respectively. Eight patients experienced relapse IE during follow-up of which seven initially received conservative treatment. Conclusion IE due to C. acnes predominantly concerns males with prosthetic heart valves. The diagnostic process in C. acnes IE is difficult due to its atypical presentation, with frequent absence of fever and inflammatory parameters. Meanwhile, blood cultures remain negative in approximately half of the patients. Moreover, the time to positivity of blood cultures is one week, which further delays the diagnostic process. Redo surgery is required in a high percentage of patients. Funding Acknowledgement Type of funding sources: None.

A Comparative Study on Removal of Appendectomy Specimen during Laparoscopy

This study included 151 patients and compared four techniques for appendectomy specimen removal during laparoscopy in a tertiary health centre. An endo bag was the most common removal technique which is preferred in the elderly, whereas, direct removal is preferred in younger patients (p=0.045). A lower median CRP level was observed in the powdered glove group (p=0.025), and median values of hospital stay were longer in powder-free and powdered glove groups (p<0.001). In comparing the powder-free glove group and powdered glove group, there was only a difference in median hospital stays, and the median level was higher in the powdered glove group. The present study's results show direct removal is the best method because of the reduced need for catheters during surgery and the short hospital stay. However, powdered gloves technique is preferred method in cases with less inflammation, though, it prolongs the need for drainage catheter use and length of hospital stay. Therefore, we emphasise that removal via powdered gloves is the worst technique among the four techniques. Key Words: Appendectomy, Appendicitis, Laparoscopy, Morbidity, Readmission.

23 Predictive factors of hip involvement in juvenile idiopathic arthritis

Abstract Background Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Hip involvement is a common problem in JIA patients and is associated with functional disability and poor outcomes. Intensive therapy is required to avoid replacement surgery. With few studies in the literature, the predictive factors of hip involvement are still unknown. Objectives To identify the clinical, biological characteristic of patients with hip involvement and determine the risk factors associated. Methods A cross-sectional study including children with JIA according to the International League of Associations for Rheumatology (ILAR). The recorded data included sociodemographic features, disease characteristics (subtype disease, duration, and juvenile arthritis disease activity score (JADAS) as well as treatment modalities. Regarding coxitis, we collected radiographs, ultrasound (US), and magnetic resonance imaging (MRI) of the hip when performed. Coxitis was defined by clinical (limited range of motion) and/or radiographic findings (destruction, synovitis, bone marrow oedema). Results Thirty-five patients (20 females) with a median age of 12 years (5–18) and disease duration 3 years (0.25–15) were recruited. The patient's distribution of JIA subtypes were oligoarticular (n = 13), enthesitis-related arthritis (n = 9), polyarticular (n = 4) (negative rheumatoid factor in 3 patients), undifferentiated (n = 4), psoriasis-arthritis (n = 4) and systemic-onset (n = 1). ESR and CRP median values were 15 mm/h (0–63) and 2 mg/l (0–47); respectively. DMARDS was admitted to 16 patients Sixteen patients [Methotrexate (n = 10), biological agent (n = 3), biological agent and methotrexate (n = 2), salazopyrine (n = 1)]. Sixteen patients (45.71%) developed coxitis (radiographic (n = 8), MRI (n = 5) and US findings (n = 3)) with limited range of movement in eight (50%) and radiological evidence of hip damage in 10 (62.5%). Hip involvement was associated with a longer disease duration (p = 0.051). JADAS of patients with coxitis was higher (Mean 8.35 vs 7.05) but not significant (p = 0.565). Higher CRP and ESR values were found in patients with coxitis (mean 8.39 mg/l vs 6.83 mg/l, 22.29 mm/h vs 16.37 mm/h respectively) but not significant (p = 0.718, p = 0.287 respectively). No associations were found between hip involvement and BMI (p = 0.233), age-onset (p = 0.496), JIA subtype (p = 0.509) and sex (p = 0.767). Conclusion Our study shows that long disease duration exposes to a higher risk of hip involvement in children with JIA. Active disease and biological inflammatory syndrome could be associated risk factors. Studies with larger sample size are needed to draw definite causal associations.

Динаміка показників імунологічного статусу та ліпідного обміну у хворих на хронічну ішемічну хворобу серця в зіставленні з розвитком серцево-судинних подій протягом тривалого спостереження

Мета роботи – оцінити зв’язок динаміки імунологічних показників і даних обміну ліпідів та ліпопротеїнів крові у хворих на хронічну ішемічну хворобу серця (ІХС) з розвитком серцево-судинних подій порівняно з пацієнтами з ІХС без таких подій протягом 6,5 року спостереження.Матеріали і методи. Хворі на ІХС зі стабільною стенокардією були розподілені на дві групи: до першої групи (n=46) увійшли пацієнти з хронічною ІХС без перенесених серцево-судинних подій за час спостереження, до другої групи (n=36) – пацієнти з хронічною ІХС з виникненням таких подій за 6,5 року спостереження. Матеріалом імунологічного дослідження була периферична венозна кров. Для визначення показників клітинного і гуморального вродженого та адаптивного імунітету в сироватці крові й супернатантах мононуклеарних клітин використовували імуноферментний аналіз. Результати та обговорення. Зіставлення динаміки показників Т-клітинного імунітету: в другій та першій групах динаміка медіан рівня Т-супресорів (CD8) – з 22 до 33 % (р=0,018) проти з 27 до 33 % (р=0,10), кількості лімфоцитів зі схильністю до апоптозу в другій та першій групах – з 18 до 27 % (р=0,11) проти з 12 до 29 % (р=0,002). Між пацієнтами з хронічною ІХС з розвитком серцево-судинних подій упродовж 6,5 року порівняно з пацієнтами без подій динаміка медіан рівня С-реактивного білка відповідно була такою – з 6,7 до 7,8 мг/л (р=0,043) проти з 3,2 до 3,8 мг/л (р=0,024), вмісту інтерлейкіну-6 (ІЛ-6) у мононуклеарних клітинах – з 2239 до 5788 пг/мл (р=0,47) проти з 2127 до 5544 пг/мл (р=0,005), ІЛ-8 у мононуклеарних клітинах – з 2305 до 3536 пг/мл (р=0,028) проти з 1980 до 3820 пг/мл (р=0,0004), протизапального ІЛ-10 у мононуклеарних клітинах – з 95 до 44 пг/мл (р=0,69) проти з 220 до 68 пг/мл (р=0,97). У пацієнтів другої групи порівняно з першою динаміка медіан рівнів загального холестерину становила відповідно з 6,9 до 6,0 ммоль/л (р=0,07) проти з 5,9 до 6,5 ммоль/л (р=0,15), тригліцеридів – з 2,2 до 1,1 ммоль/л (р=0,08) проти з 1,9 до 1,5 ммоль/л (р=0,030), холестерину ліпопротеїнів високої щільності – з 1,15 до 1,28 ммоль/л (р=0,89) проти з 1,10 до 1,40 ммоль/л (р=0,0005), динаміка медіан ступеня перекисної модифікації ліпопротеїнів: з 7,1 до 2,6 ум. од. (р=0,14) проти з 5,4 до 3,1 ум. од. (р=0,0008), вільнорадикального окиснення білків – з 3,3 до 5,0 (р=0,028) проти з 4,6 до 5,1 ум. од. (р=0,54).Висновки. У хворих на хронічну ІХС упродовж 6,5 року статистично значуще зростає активність імунного запалення. Розвиток серцево-судинних подій за цей період не супроводжується особливостями збільшення показників імунного запалення, особливостями змін досліджуваних показників гуморальної ланки набутого імунітету та показників системи фагоцитів порівняно з пацієнтами без таких подій. Виникнення серцево-судинних подій супроводжується більшою активацією Т-лімфоцитів та меншим зростанням кількості лімфоцитів зі схильністю до апоптозу, статистично значущим зростанням за цей період активності вільнорадикального окиснення білків порівняно з пацієнтами без таких ускладнень. Відсутність серцево-судинних подій поєднується зі статистично значущим зростанням рівня холестерину ліпопротеїнів високої щільності на тлі терапії статинами.

Retinal drusen counts are increased in inflammatory bowel disease, and with longer disease duration, more complications and associated IgA glomerulonephritis

Retinal drusen are deposits of inflammatory proteins that are found in macular degeneration and glomerulonephritis and result, in part, from complement activation. This was a cross-sectional observational study of individuals with inflammatory bowel disease (IBD) recruited from a Gastroenterology clinic who underwent non-mydriatic retinal photography. Deidentified images were examined for drusen, and drusen counts and size were compared with matched controls, and examined for clinical associations. The cohort with IBD comprised 19 individuals with ulcerative colitis, 41 with Crohn’s disease and three with indeterminate colitis, including 34 males (54%) and an overall median age of 48 (IQR 23) years. Their median IBD duration was 7 (IQR 10) years, median CRP level was 7 (IQR 14) mg/L, and 28 (44%) had complications (fistula, stricture, bowel resection etc.), while 28 with Crohn’s disease (68%) had colonic involvement. Drusen counts were higher in IBD than controls (12 ± 34, 3 ± 8 respectively, p = 0.04). Counts ≥ 10 were also more common (14, 22%, and 4, 6%, p = 0.02, OR 4.21, 95%CI 1.30 to 13.63), and associated with longer disease duration (p = 0.01, OR 1.06, 95%CI 1.00 to 1.13), an increased likelihood of complications (p = 0.003, OR 6.90, 95%CI 1.69 to 28.15) and higher CRP levels at recruitment (p = 0.008, OR1.02, 95%CI 1.00 to 1.05). Increased retinal drusen were found in all four individuals with Crohn’s disease and IgA glomerulonephritis. IBD and drusen may share pathogenetic mechanisms and underlying risk factors such as complement activation.

Serum C-reactive Protein &amp; Ferritin Level in Patients with Maintenance Hemodialysis

Background: Hemodialysis is the widely used renal replacement therapy for end stage renal disease. Chronic inflammation isvery common in patients with maintenance hemodialysis. There are several markers to assess the inflammatory status. Some ofthese markers strongly predict the mortality &amp; morbidity among these patients. Objectives: This study was carried out to determine serum C-reactive protein and ferritin level inpatients with maintenancehemodialysis (MHD). Methods: This cross-sectional study was carried out in the Department of Biochemistry, Dhaka medical college, Dhaka fromthe period of July 2018 to June2019. In this study, thirty patients on MHD were taken from the dialysis unit,Department of Nephrology, Dhaka Medical College Hospital, Dhaka. For betterassessment another age and sex matched thirty healthyindividual were also taken.SerumCRP and ferritin level of all participants were measured and all values wereanalyzedstatistically. Results: Serum C-reactive protein level was found to be higher than normal in 70%of MHD patients. Median CRP level wassignificantlyhigher in hemodialysis group (13.9 mg/L) when compared with controls (1.74 mg/L). 80% MHD patient hadserum ferritin value &gt;500 μg/L. Median serum ferritin level was alsosignificantly higher in hemodialysis patients comparedwith controls (1342 μg/L vs 51 μg/L). Serum CRP had significant positivecorrelation with serum ferritin in high CRP group ofMHD patients (r= 0.658, p= 0.001). Conclusion: Serum CRP and ferritin level were higher in MHD patients than control. Serum CRP had linear positive relationwith serum ferritin in MHD patients having high CRP value.

MO181: Clinical Characteristics and Short-Term outcomes of Hemodialysis Patients with SARS-COV-2 Infection: The Experience of a Covid Nephrology Unit

BACKGROUND AND AIMSSARS-CoV-2 pandemic is pressuring healthcare systems worldwide. Disease outcomes in certain subgroups of patients, such as nephropathic patients, are still scarce. Patients with chronic kidney disease (CKD) and on haemodialysis (HD) are at risk of a more severe disease course and worst outcomes. Here, we aimed to describe the characteristics and outcomes of CKD and HD patients with SARS-CoV-2 infection, admitted to the Covid Nephrology Unit in the first three pandemic waves, analysing mortality rate and risk factors for mortality in this subgroup of patients.METHODA Covid Nephrology Unit was organized in March 2020 to manage the high number of CKD and HD patients with SARS-CoV-2 infection. Several ‘spoke’ units were also set to manage HD asymptomatic patients (Hi Hotel and ‘Villa Luce’ Dialysis Center) or with mild symptoms (‘Miulli Hospital’-Acquaviva delle Fonti and ‘Fallacara Hospital’—Triggiano). Clinical and laboratory data in several timepoints were collected using electronic medical records. Primary outcome was to assess the mortality rate. Moreover, we analysed the trend of inflammatory markers in the first 7 days after hospital admission between survivors and non-survivors; finally, risk factors for mortality were analysed by logistic regression.RESULTSFrom March 2020 to May 2021, a total of 221 patients were admitted to the Covid Nephrology Unit; among these, 112 patients on chronic haemodialysis, 21 with acute kidney injury (AKI), 58 with CKD, 24 kidney transplant recipients and 6 patients on peritoneal dialysis (PD). Median age was 71 years (IQR 62.5–80), while male gender predominated (61.5%). Main comorbidities were arterial hypertension (81%), diabetes mellitus (41.8%) and cardiovascular disease (CVD, 60.6%). At admission, 13.2% of patients required non-invasive ventilatory (NIV) support (CPAP, BiPAP) and about 60% presented interstitial pneumonia at CT scan. A total of 80 patients (36.1%) died during hospital stay with a medium length of stay of 15.8 days. In the first 7 days, 29 patients presented respiratory failure requiring transfer to ICU. Conversely, 100 patients were discharged at home, while 48 patients were transferred to the spoke units (39 patients at Miulli and Fallacara Hospitals, 9 patients at Hi Hotel). Compared to survivors, patients who died were older (median age 75.5 versus 66 years, P < .001), characterized by more comorbidities (diabetes mellitus 54.5% versus 35.2%, P = .01; CVD 81.1% versus 51.4%, P < .001; chronic obstructive pulmonary disease (COPD, 41.5% versus 19%, P = .01; peripheral vasculopathy 58.4% versus 34.2%, P = .01) and more severe respiratory compromission at hospital admission (patients in NIV, 22.6% versus 8.1%, P = .005). As shown in Table 1, in the first 7 days of hospital stay, a significant increase in WBC (8.29 versus 12.6 × 106P < .001) was described in the non-survivor group; similarly, inflammatory markers such as CRP and IL-6 did not improve in the non-survivors at day 7 (CRP 81.8 versus 85.7 mg/L, P = .62; IL-6 63.1 versus 79.4 pg/mL, P = .84), while they significantly improved in survivors (median CRP 42.5 versus 10.1 mg/L, P < .001; median IL-6 32.3 versus 13.7 pg/mL, P = .01). In a multivariate logistic regression model, age (OR 1.062, 95% CI 1.007–1.119, P = .025), history of CVD (OR 8.308, 95%CI 1.704–40.499, P = .009) and dyspnoea at hospital admission (OR 9.465, 95%CI 1.231–72.79, P = .031) were associated with risk of mortality in this population. CONCLUSIONTo our knowledge, this is the largest study analyzing characteristics and outcomes of CKD and hemodialysis patients to date. A wide heterogeneity of severity of disease has been documented in our cohort; we documented a higher mortality rate in this cohort of patients compared to general population. The presence of several comorbidities, a more severe disease at hospital admission and the persistence of elevated inflammatory markers during hospital stay are risk factors for mortality.

Effect of Ramadan intermittent fasting on inflammatory markers, disease severity, depression, and quality of life in patients with inflammatory bowel diseases: A prospective cohort study

BackgroundIntermittent fasting (IF) during the month of Ramadan is part of the religious rituals of Muslims. The effect of intermittent fasting on disease activity in inflammatory bowel diseases (IBD) is still unknown. This is the first study to assess the effect of IF during Ramadan on inflammatory markers in patients diagnosed with IBD. The effects on clinical disease activity, quality of life, and levels of depression were also assessed.MethodsPatients diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD) who intended to observe Ramadan fasting were recruited. The following were assessed immediately before and at the end of Ramadan: Serum CRP and stool calprotectin, partial Mayo score, Harvey Bradshaw index (HBI), Simple IBD questionnaire (SIBDQ), and Hamilton depression scale questionnaire.Results80 patients diagnosed with IBD were recruited (60 UC, 20 CD). Serum CRP and stool calprotectin did not show a significant change before vs after fasting (median CRP 0.53 vs 0.50, P value = 0.27, Calprotectin 163 vs 218 respectively, P value = 0.62). The partial Mayo score showed a significant rise after fasting (median 1 before vs 1 after fasting, mean: 1.79 vs 2.33 respectively, P value = 0.02). Harvey-Bradshaw index did not show a significant change after fasting (median 4 vs 5, P value = 0.4). Multiple linear regression revealed that older age and a higher baseline calprotectin were associated with a higher change in Mayo score after fasting (P value = 0.02 and P value = 0.01, respectively). No significant change was detected in SIBDQ or Hamilton depression scale scores.ConclusionsIn patients diagnosed with UC, IF during Ramadan was associated with worsening of clinical parameters, the effect was more pronounced in older patients and those with higher baseline calprotectin levels. However, IF during Ramadan was not associated with an adverse effect on objective inflammatory markers (CRP and calprotectin).

The Role of C-Reactive Protein as a Triage Tool for Pulmonary Tuberculosis in Children.

C-reactive protein (CRP) has shown promise as a triage tool for pulmonary tuberculosis (TB) in adults living with the human immunodeficiency virus. We performed the first assessment of CRP for TB triage in children. Symptomatic children less than 15 years old were prospectively enrolled in Kampala, Uganda. We completed a standard TB evaluation and measured CRP using a point-of-care assay. We determined the sensitivity and specificity of CRP to identify pulmonary TB in children using 10 mg/L and 5 mg/L cut-off points and generated a receiver operating characteristic (ROC) curve to determine alternative cut-offs that could approach the target accuracy for a triage test (≥90% sensitivity and ≥70% specificity). We included 332 children (median age 3 years old, interquartile range [IQR]: 1-6). The median CRP level was low at 3.0 mg/L (IQR: 2.5-26.6) but was higher in children with Confirmed TB than in children with Unlikely TB (9.5 mg/L vs. 2.9 mg/L, P-value = .03). At a 10 mg/L cut-off, CRP sensitivity was 50.0% (95% confidence interval [CI], 37.0-63.0) among Confirmed TB cases and specificity was 63.3% (95% CI, 54.7-71.3) among children with Unlikely TB. Sensitivity increased to 56.5% (95% CI, 43.3-69.0) at the 5 mg/L cut-off, but specificity decreased to 54.0% (95% CI, 45.3-62.4). The area under the ROC curve was 0.59 (95% CI, 0.51-0.67), and the highest sensitivity achieved was 66.1% at a specificity of 46.8%. CRP levels were low in children with pulmonary TB, and CRP was unable to achieve the accuracy targets for a TB triage test.

Nurse-led vascular risk assessment in a regional Victorian Indigenous primary care diabetes clinic: An integrated Diabetes Education and Eye disease Screening [iDEES] study.

The aim was to describe vascular risk factors in Australian adults with diabetes attending an Indigenous primary care nurse-led diabetes clinic. This was a cross-sectional descriptive single-site study. Vascular risk factor data were extracted from the electronic health records of participants in the nurse-led integrated Diabetes Education and Eye disease Screening (iDEES) study at a regional Victorian Indigenous primary health-care clinic between January 2018 and March 2020. Of 172 eligible adults, 135 (79%) provided data. Median (IQR) age was 56 (46-67) years; 89% were Indigenous; 95% had Type 2 diabetes of median (IQR) duration of 6 (2-12) years and 48 (36%) were male. Median HbA1c, blood pressure, cholesterol (total; LDL and HDL), triglycerides, eGFR, CRP and BMI were 8.0% (64 mmol/mol), 127/78 mm Hg, 4.2; 1.9; 1.1 mmol/L, 2.3 mmol/L, 89 ml/min/1.73 m2 , 7.0 mg/L and 32.4 kg/m2 . Of nine clinical risk factors, the median (IQR) number of risk factors at target was 4 (3-5) for women and 3 (2-5) for men, pχ2 =0.563. Clinical targets for BMI, HbA1c, blood pressure, triglycerides, total cholesterol, LDL cholesterol, urine albumin: creatinine ratio, HDL cholesterol and smoking were met by 14%, 34%, 38%, 39%, 44%, 52%, 54%, 62% and 64%, respectively. A nurse-led model of integrated clinical risk factor assessment and diabetes education identified suboptimal levels of clinical risk factor control for avoiding diabetes chronic complications amongst Australian adults with diabetes in an Indigenous primary care setting. A nurse-led model of diabetes care integrating clinical risk factor assessment into a diabetes education service is achievable. Understanding by stakeholders, including people with diabetes, their clinicians and health services, of the importance of regular monitoring of risk factors impacting diabetes complications is important. The novel nurse-managed iDEES primary-care model of care can assist. This study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12618001204235).

Characterization of antimicrobial use and co-infections among hospitalized patients with COVID-19: a prospective observational cohort study

PurposeTo investigate antimicrobial use and primary and nosocomial infections in hospitalized COVID-19 patients to provide data for guidance of antimicrobial therapy.MethodsProspective observational cohort study conducted at Charité–Universitätsmedizin Berlin, including patients hospitalized with SARS-CoV-2-infection between March and November 2020.Results309 patients were included, 231 directly admitted and 78 transferred from other centres. Antimicrobial therapy was initiated in 62/231 (26.8%) of directly admitted and in 44/78 (56.4%) of transferred patients. The rate of microbiologically confirmed primary co-infections was 4.8% (11/231). Although elevated in most COVID-19 patients, C-reactive protein and procalcitonin levels were higher in patients with primary co-infections than in those without (median CRP 110 mg/l, IQR 51–222 vs. 36, IQR 11–101, respectively; p < 0.0001). Nosocomial bloodstream and respiratory infections occurred in 47/309 (15.2%) and 91/309 (29.4%) of patients, respectively, and were associated with need for invasive mechanical ventilation (OR 45.6 95%CI 13.7–151.8 and 104.6 95%CI 41.5–263.5, respectively), extracorporeal membrane oxygenation (OR 14.3 95%CI 6.5–31.5 and 16.5 95%CI 6.5–41.6, respectively), and haemodialysis (OR 31.4 95%CI 13.9–71.2 and OR 22.3 95%CI 11.2–44.2, respectively). The event of any nosocomial infection was significantly associated with in-hospital death (33/99 (33.3%) with nosocomial infection vs. 23/210 (10.9%) without, OR 4.1 95%CI 2.2–7.3).ConclusionsPrimary co-infections are rare, yet antimicrobial use was frequent, mostly based on clinical worsening and elevated inflammation markers without clear evidence for co-infection. More reliable diagnostic prospects may help to reduce overtreatment. Rates of nosocomial infections are substantial in severely ill patients on organ support and associated with worse patient outcome.

Incidence and Clinical Features of Pneumomediastinum and Pneumothorax in COVID-19 Pneumonia.

BackgroundPneumothorax (PTX) and pneumomediastinum (PM), collectively termed here “air leak”, are now well described complications of severe COVID-19 pneumonia across several case series. The incidence is thought to be approximately 1% but is not definitively known.ObjectivesTo report the incidence and describe the demographic features, risk factors and outcomes of patients with air leak as a complication of COVID-19.MethodsA retrospective observational study on all adult patients with COVID-19 admitted to Watford General Hospital, West Hertfordshire NHS Trust between March 1st 2020 and Feb 28th 2021. Patients with air leak were identified after reviewing both chest radiographs (CXRs) and axial imaging (CT Thorax) with confirmatory radiology reports inclusive of the terms PTX and/or PM.ResultsAir leak occurred with an incidence of 0.56%. Patients with air leak were younger and had evidence of more severe disease at presentation, including a higher median CRP and number of abnormal zones affected on chest radiograph. Asthma was a significant risk factor in the development of air leak (OR 13.4 [4.7-36.4]), both spontaneously and following positive pressure ventilation. CPAP and IMV were also associated with a greater than six fold increase in the risk of air leak (OR 6.4 [2.5-16.6] and 9.8 [3.7-27.8] respectively). PTX, with or without PM, in the context of COVID-19 pneumonia was almost universally fatal whereas those with alone PM had a lower risk of death.ConclusionDespite the global vaccination programme, patients continue to develop severe COVID-19 disease and may require respiratory support. This study demonstrates the importance of identifying that deterioration in such patients may be resultant from PTX or PM, particularly in asthmatics and those managed with positive pressure ventilation.

Reduced fixed dose tocilizumab 400 mg IV compared to weight-based dosing in critically ill patients with COVID-19: A before-after cohort study

BackgroundInterleukin-6 inhibitors reduce mortality in severe COVID-19. British Columbia began using tocilizumab 8 mg/kg (maximum 800 mg) in January 2021 in critically ill patients with COVID-19, but due to drug shortages, decreased dosing to 400 mg IV fixed dose in April 2021. The aims of this study were twofold: to compare physiological responses and clinical outcomes of these two strategies, and examine the cost-effectiveness of treating all patients with 400 mg versus half the patients with 8 mg/kg and the other half without tocilizumab.MethodsThis was a single-centre, before-after cohort study of critically ill COVID-19 patients treated with tocilizumab, and a control cohort treated with dexamethasone only. Physiological responses and clinical outcomes were compared between patients receiving both doses of tocilizumab and those receiving dexamethasone only. We built a decision tree model to examine cost-effectiveness.Findings152 patients were included; 40 received tocilizumab 8 mg/kg, 59 received 400 mg and 53 received dexamethasone only. Median CRP fell from 103 mg/L to 5.2 mg/L, 96 mg/L to 6.8 mg/L and from 81.3 mg/L to 48 mg/L in the 8 mg/kg, 400 mg tocilizumab, and dexamethasone only groups, respectively. 28-day mortality was 5% (n=2) vs 8% (n=5) vs 13% (n=7), with no significant difference in all pair-wise comparison. At an assumed willingness-to-pay threshold of $50,000 Canadian per life-year, utilizing 400 mg for all patients rather than 8 mg/kg for half the patients is cost-effective in 51.6% of 10,000 Monte Carlo simulations.InterpretationBoth doses of tocilizumab demonstrated comparable reduction of inflammation with similar 28-day mortality. Without consideration of equity, the net monetary benefits of providing 400 mg tocilizumab to all patients are comparable to 8 mg/kg to half the patients. In the context of ongoing drug shortages, fixed-dose 400 mg tocilizumab may be a practical, feasible and economical option.FundingThis work was supported by a gift donation from Hsu & Taylor Family to the VGH Foundation, and the Yale Bernard G. Forget Scholarship.

NON-IMMUNE MEDIATED MUSCULOSKELETAL DISEASE IN CROHN’S DISEASE PATIENTS BEING EVALUATED FOR INFLAMMATORY SPONDYLOARTHRITIS - A PILOT STUDY

BACKGROUNDMusculoskeletal (MSK) disease is the most common extra-intestinal manifestation of inflammatory bowel disease (IBD). The emphasis in the published literature has been on the inflammatory arthritis associated with IBD, spondyloarthritis (SpA). There is a lack of data regarding common, non-inflammatory MSK diseases such as osteoarthritis and fibromyalgia. This distinction is important, as these two conditions have different prognoses, require different clinical approaches and management.OBJECTIVETo evaluate the prevalence of non-inflammatory MSK disease in a cohort of Crohn’s disease (CD) patients.METHODSThis was a cross-sectional study of a validated CD cohort from a single center registry in New York City conducted from 9/2019 - 1/2021. Recruitment was limited due to the COVID-19 Pandemic. Patients were sent a four question MSK survey (Figure 1) addressing peripheral joint and back symptoms. Those who answered positively to any question were considered to have MSK symptoms. All patients underwent one study visit with a rheumatologist that included: 66/68 tender/swollen joint count (TJC/SJC), Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC), Bath Ankylosing Spondylitis Metrology Index (BASMI), American College of Rheumatology fibromyalgia criteria, ESR and CRP. Disease activity was measured via a modified Ankylosing Spondylitis Disease Activity Score (ASDAS), Harvey Bradshaw Index (HBI), and Inflammatory Bowel Disease Questionnaire (IBD-Q).RESULTS26 CD patients participated. Median age was 45.6±17.7 years, 35% were male, median disease duration was 17.7±14.2 years and 73% were on immunomodulatory agents for CD. Median values (range) for the following physical exam and disease features were: TJC 10.8±13.2 (0-68), SJC 0.9±2.2 (0-66), SPARCC 2.8±3.1 (0-16), BASMI 1.5±1.0 (0-10, higher values: more motion limitation) ASDAS 1.5±0.9 (<1.3: inactive disease, >2.1: high disease activity), HBI 6.8±3.5 and IBD-Q 159±36. Median ESR and CRP were 18.9±22.2 mm/hr (normal 0-22) and 0.6±0.5 mg/dL (normal<0.7), respectively. 16/26 (62%) reported MSK symptoms. 7/16 (43.8%) had features of SpA, while 9/16 (56.3%) did not have evidence by history or exam of SpA and were therefore determined to have non-inflammatory MSK disease. 13/26 (50%) met fibromyalgia diagnostic criteria.CONCLUSIONMSK conditions were very common in this pilot cohort. Though features of SpA were present in almost half of patients, non-inflammatory MSK disease was present in the majority of those with MSK symptoms. While both rheumatologists and gastroenterologists need to recognize the importance of SpA, it is additionally essential to understand that the most common MSK disease in IBD may be non-inflammatory, which has distinct implications for management. Future studies should examine the prevalence of these conditions in larger cohorts of IBD patients.

P411 Stable pharmacokinetics and biochemical markers of inflammatory bowel disease activity: Results from a real-world adalimumab biosimilar switching program

Abstract Background Biosimilars have delivered significant cost savings, increasing access to biologics for many patients. While numerous studies have demonstrated no difference in efficacy between originators and biosimilars, the impact of switching between originator and biosimilar adalimumab on drug levels and disease activity in real world cohorts remains largely unknown. Methods We conducted a retrospective observational cohort study of, 392 patients with IBD (347 (89%) CD, 45 (11%) UC) who had switched from Humira to the biosimilar, Idacio, between February - November, 2021. Therapeutic drug monitoring was carried out using a commercially available, drug sensitive ELISA (LISA TRACKER, Theradiag). Therefore, antidrug antibodies could only be detected in the setting of low or absent serum drug concentrations. Drug level data was parametric and analysed by paired student t test and Pearson correlation coefficient. CRP data was analysed by Wilcoxon test. Data was analysed using GraphPad Prism. Results The baseline characteristics of the study participants are presented in the table., 96 patients had paired adalimumab drug levels before and after the switch. There was no difference between median adalimumab drug levels before and after the switch (9.5 vs, 9.2 ug/mL, p=0.67). Furthermore, drug levels were positively correlated before and after switching demonstrating similar levels at both time points for most patients (correlation co-efficient, 0.47, p &amp;lt;, 0.0001) (Figure, 1). Prior to switching, no patients had detectable antidrug antibodies. Following switch, one patient (1%) developed high-titre antidrug antibodies and undetectable drug levels. Prior to switch their levels were, 14, without detectable antidrug antibodies CRP levels were available for, 163 patients before and after the switch, with no difference in median CRP at either time point (1 vs, 1mg/L p=0.60). 33 (8%) patients experienced injection site pain with Idacio and therefore, switched back to Humira. The annual cost saving to the UK National Health Service for patients on weekly and every other week switched to Idacio is £5096 and £2548, respectively Conclusion Our study demonstrates stable pharmacokinetics and biochemical disease activity amongst a significant cohort of patients switching from originator to biosimilar adalimumab as part of a real-world switching program. However, a small proportion of patients did not tolerate Idacio due to injection site pain. There are clear financial benefits in carrying out non-medical, biosimilar switching programs but further work is needed to evaluate the effect on clinical and endoscopic disease activity in a real-world setting.

P321 Mucosal Healing and Clinical remission after Treatment with Adalimumab in Small Intestinal Crohn’s Disease (SIMCHA study): final results from a prospective, open-label, single-arm study

Abstract Background Endoscopic mucosal healing is a key treatment target in inflammatory bowel disease (IBD). The aim of this study was to investigate small bowel (SB) mucosal healing using video capsule endoscopy (VCE) in patients with Crohn’s disease (CD) following, 24 weeks of adalimumab therapy. Methods In this prospective study, moderate to severe SB involvement CD patients were enrolled, defined by a Lewis score on VCE at diagnosis &amp;gt;, 790 in at least one tertile. All patients were treated with adalimumab monotherapy at the standard dosing for CD for, 24 weeks prior to undertaking the follow-up second VCE. The primary outcome was the endoscopic healing defined as a Lewis score (LS) &amp;lt;, 350, whereas partial response was defined as a &amp;gt;, 50% decrease from baseline in LS. Secondary outcomes included the remission in the clinical symptoms (Harvey Bradshaw Index, HBI &amp;lt;, 4) and biomarkers (fecal calprotectin, FC &amp;lt;, 200 ug/g, and c-reactive protein, CRP &amp;lt;, 5 mg/l). Results A total of, 59 CD patients were screened at McGill University Health Centre between November, 2011 and October, 2021;, 15 patients were met the eligibility criteria and were enrolled. The median age at inclusion was, 46 years (IQR, 28–51), 8 patients (53.3%) had ankylosing spondylitis. The most frequent locations of CD on VCE findings were the proximal-mid ileum (93.3%) and jejunum (73.3%). Primary outcome; complete endoscopic healing was observed in, 8 patients (53.3%, p=0.002, OR for remission = 2.14, 95%CI:, 1.25–3.68), and partial response in an additional, 5 patients (33.3%) after, 24 weeks. The median total Lewis score was decreased significantly compared to the baseline (1,912 vs., 337, p=0.0005). Secondary outcomes; the HBI at baseline was elevated (&amp;gt;, 4) in, 11 patients. Post-treatment HBI was consistent with clinical remission in all cases (11/15 vs., 0/15, p &amp;lt;0.0001 OR clinical remission = 0.27,95%CI:0.12–0.62). Nine patients who had baseline CRP elevation had achieved normal CRP after treatment, and the median CRP was significantly decreased from, 7.3 mg/L (1.8 -18.0) to, 1.6 mg/L (IQR, 1.0 –, 3.2), p=0.025. However, there were no significant changes in FC pre-and post-treatment. In addition, baseline VCE demonstrated ulcerated SB strictures in, 3 patients, 2 had non-ulcerated strictures on the second VCE. No capsule retention or other adverse events were observed. Conclusion Adalimumab led to significant improvement of small intestinal endoscopic healing in Crohn’s disease, with, 53% achieving complete healing.

P393 Efficacy and Safety of Induction Therapy With Calcineurin Inhibitors in Combination With Ustekinumab for acute severe colitis

Abstract Background Ulcerative colitis is a chronic inflammatory bowel disease., 20% of patients will experienced acute severe colitis during their life. In acute severe colitis, when IV steroids failed, two strategies can be used with equivalent efficacy: Ciclosporin and Infliximab. Recently, Pellet et al reported the interest of association ciclosporin – vedolizumab. Regarding results from Varsity trial, more patients are treated before a CAG with vedolizumab. Recently, UNIFI trial showed the interest of ustekinumab in UC patients. So, it should be interesting to analyze the interest of the association Ciclosporin -Ustekinumab in case of acute severe ulcerative colitis. In this study, we retrospectively evaluated the clinical response and the rate of colectomy when we used anticalcineurin and Ustekinumab in acute severe colitis refractory to IV steroids. Methods All patients with acute severe colitis who failed to IV steroid and who were treated with calcineurin inhibitor and Ustekinumab, can be included. They were treated with a, 6mg/kg infusion and then a, 90mg subcutaneous injection every, 8 weeks. Eight referral French center and a Switzerland referral center were involved in this study. The primary endpoint was clinical response at, 6 months. We also evaluated the rate of colectomy and survival without Ustekinumab discontinuation. We reported also adverse events in this cohort. Results Eleven patients were included., 82% were women, with a median age of, 32.2 years (range, 25.5–36.5 y). The median disease duration was, 8.2 years (range, 3–9.5 y). Ten patients failed to Infliximab and, 9 to Vedolizumab. At inclusion, median Lichtiger score, Mayo score and CRP were respectively, 13,4 [IC95, 12.5–14.5], 10.6 [IC95, 10–11.5] et de, 24.5 mg/L [IC95, 4.5–35.7mg/l]. The mean Endoscopic Mayo score was, 2.6 +/-0.7. The median time between beginning of Calcineurin inhibitor and Ustekinumab was, 22 days (minimum, 6d, maximum, 128d). Median follow-up was, 11 months. None of the patients underwent colectomy at, 6 months. The mean full Mayo score was significantly lower during the follow-up (10.6 at baseline and, 1.0 at, 6 months; p = 0.005). The mean CRP level was significantly reduced (from, 24.5 mg / L [CI95, 4.5–35.7] to, 2.6 mg / L [2–3.1], p = 0.02). Only one patient stopped ustekinumab at the end of follow-up. Two patients required treatment optimization. Tolerance to treatment was well with only one case of alopecia described without withdrawal of treatment. Conclusion In this retrospective study including patients hospitalized for IV Steroid-resistant acute severe colitis, the sequence of treatment with induction anti-calcineurin with ustekinumab therapy appears to be effective and well tolerated. These results need to be confirmed on a larger number of patients.

Is C-reactive protein-albumin ratio or neutrophil-lymphocyte ratio a better indicator to predict in-hospital mortality in traumatic brain injury?

Neutrophil-lymphocyte ratio (NLR) and C-reactive protein-albumin ratio (CAR) are simple and objective markers of inflammatory responses. However, there are no studies in the literature evaluating these two markers together in traumatic brain injury (TBI). Therefore, this study aimed to examine whether CAR or NLR is a better biomarker for predicting in-hospital mortality in patients with TBI. A total of 257 consecutive patients admitted to the hospital between January 2016 and December 2021 were included in the study. The files of all patients aged >18 years with TBI were retrospectively reviewed. Clinical characteristics, Glasgow Coma Scale, and patient data during hospital stay were recorded. Definitive diagnosis was made using computed brain tomography. Routine blood tests were performed in the first 12-24 h of hospitalization. Laboratory results of patients with and without in-hospital mortality were comparatively analyzed. According to the Mann-Whitney U-test, median CRP, CAR, NLR, WBC, monocyte, neutrophil, RDW-CV, RDW-SD, and platelet values were significantly higher, whereas median albumin and RBC values were significantly lower in patients with in-hospital mortality. Student's t-test showed that the mean hemoglobin level was significantly lower in patients with in-hospital mortality compared to other patients. Univariate logistics regression model revealed that age, albumin, CRP, CAR, NLR, WBC, monocyte, neutrophil, RBC, RDW-CV, RDW-SD, and hemoglobin were the factors predicting mortality. However, in the multivariate logistic regression model, only age, albumin, CAR, and WBC were the factors predicting mortality. Areas under the curve were 0.891 for CAR (95% GA, 0.847-0.935), 0.759 for WBC (95% GA, 0.696-0.823), and 0.671 for NLR (95% GA, 0.598-0.744). The results of this study showed that CAR has better prognostic value than NLR in predicting in-hospital mortality in patients with TBI.